Fine structure of neutrophils from turpentine-induced pleuritis in mice, simulating rheumatoid arthritis cells.

Pleural effusions were made by intrapleural turpentine installation in mice. The fine structure of inflammatory cells from the effusions was normal except for lipid inclusions. The same type of inclusion was previously found in neutrophils from pleural effusions in patients with tuberculous infection, rheumatoid disease, or carcinomatosis. The lipid inclusions observed in neutrophils from an irritative turpentine-induced pleurisy should be considered as "fatty change", and are structurally similar to the rheumatoid arthritis cells seen in patients with different diseases.     

AHRA survey. Survey on job content and salary: Part III

Part III of the AHRA Statistical Resource Committee salary survey compares the AHRA data with other studies. Comparisons are also provided between AHRA data from 1984 to 1990, highlighting trends in salary and education level, annual increases, and job satisfaction.     

The bovine immune response to Brucella abortus. II. Elimination of some sporadic serological reactions by chelation of divalent cations.

The standard agglutination tests for detecting antibody to Brucella abortus were modified by addition of chelating agents (EDTA and EGTA) to the antigens. Approximately 80% of "singleton" agglutination test reactions, negative on the diagnostic complement fixation test, obtained with cattle sera were eliminated while no decrease in titer was apparent when sera from B. abortus infected or vaccinated cattle were tested.     

Desipramine and some other antidepressant drugs decrease the major norepinephrine metabolite 3,4-dihydroxyphenylglycol-sulphate in the rat brain

Summary The O-methylated and non-O-methylated end metabolites of norepinephrine (NE) in the rat brain were measured to investigate a presumed shift in metabolism of NE from intra- to extraneuronal metabolism by uptake inhibitory antidepressant drugs. Desipramine (DMI), protriptyline and maprotiline in doses from 2.5–20 mg/kg reduced the concentration of the major non-O-methylated NE metabolite 3,4-dihydroxyphenylglycolsulphate (DOPEG-SO₄) in the whole rat brain to about 60–70% of controls, while imipramine, amitriptyline, butriptyline and clorimipramine (20 mg/kg, 21/2 h) caused no significant decrease. The major O-methylated NE metabolite free plus conjugated 3-methoxy-4-hydroxyphenylglycol (total-MOPEG) was almost unaffected by all the drugs 21/2 h after administration. At longer time intervals, however, i.e. 5 h, a high dose of DMI (10 mg/kg, s.c.) decreased total-MOPEG to 75% of controls. DOPEG-SO₄ was decreased by DMI in all brain regions examined: cortex, hippocampus, cerebellum and brain rest. ³H-normetanephrine was increased 1/2h and 1 h after intraventricular injection of ³H-dopamine, and at the same time interval both total-³H-MOPEG and ³H-DOPEG-SO₄ were decreased. Amine storage in granules was not necessary for the action of DMI since DMI retained its metabolite-lowering effects in reserpinized rats. Inhibition of NE uptake in vivo did not induce the expected increase in the major extraneuronal NE metabolite MOPEG, but only the expected decreased in DOPEG-SO₄. The reduction of both the major NE metabolites by DMI suggests a decreased metabolism and turnover of NE.Abbreviations Used NE norepinephrine - DOPEG 3,4-dihydroxyphenylglycol - DOPEG-SO₄ DOPEG sulphate ester - MOPEG 3-methoxy-4-hydroxyphenylglycol - total-MOPEG free plus conjugated MOPEG - DOPAC 3,4-dihydroxyphenylacetic acid - HVA homovanillic acid - NM normetanephrine - DA dopamine - DMI desipramine - MAO monoamine oxidase     

Chronic treatment with desipramine caused a sustained decrease of 3,4-dihydroxyphenylglycol-sulphate and total 3-methoxy-4-hydroxyphenylglycol in the rat brain

Summary The 2 major metabolites of norepinephrine (NE), 3,4-dihydroxyphenylglycol-sulphate (DOPEG-SO₄) and free plus conjugated 3-methoxy-4-hydroxyphenylglycol (total-MOPEG), both their endogenous concentrations and their accumulation from the NE-precursors ³H-tyrosine or ³H-dopamine, were determined in the whole rat brain to assess the effect of chronic treatment with desipramine (DMI), imipramine and amitriptyline. DOPEG-SO₄ was decreased 2 h and 24 h after the last administration of DMI (10 mg/kg twice daily for 4, 10 or 20 days) or imipramine (10 mg/kg twice daily for 10 days). When measured within 24 h after the last dose of DMI or imipramine, several schedules resulted in reduced accumulation of total-³H-MOPEG and ³H-NE, while ³H-NE and MOPEG were unchanged in the remaining schedules. These results indicate that DMI retains its ability to decrease NE-turnover over a period of 20 days of treatment. Forty-eight hours or 72 h after the last administration of desipramine and imipramine an overshoot was observed in NE-metabolism, consisting of increased levels of total-³H-MOPEG and endogenous total-MOPEG; DOPEG-SO₄ was some-times concomitantly increased. The overshoot was more consistent after 20 or 10 days of treatment than after 4 days of treatment. This finding, together with a tendency to partial tolerance to the metabolite decreasing effects of DMI, indicate that adaptive changes occur in the NE system after treatment for 10–20 days with DMI or imipramine.Abbreviations Used NE norepinephrine - DOPEG 3,4-dihydroxyphenylglycol - DOPEG-SO₄ DOPEG sulphate ester - MOPEG 3-methoxy-4-hydroxyphenylglycol - total-MOPEG free plus conjugated MOPEG - DOPAC 3,4-dihydroxyphenylacetic acid - HVA homovanillic acid - NM normetanephrine - DA dopamine - DMI desipramine     

New equations improve NIR prediction of body fat among high school wrestlers

STUDY DESIGN: Methodologic study to derive prediction equations for percent body fat (%BF). OBJECTIVES: To develop valid regression equations using NIR to assess body composition among high school wrestlers. BACKGROUND: Clinicians need a portable, fast, and simple field method for assessing body composition among wrestlers. Near-infrared photospectrometry (NIR) meets these criteria, but its efficacy has been challenged. METHODS AND MEASURES: Subjects were 150 high school wrestlers from 2 Midwestern states with mean +/- SD age of 16.3 +/- 1.1 yrs, weight of 69.5 +/- 11.7 kg, and height of 174.4 +/- 7.0 cm. Relative body fatness (%BF) determined from hydrostatic weighing was the criterion measure, and NIR optical density (OD) measurements at multiple sites, plus height, weight, and body mass index (BMI) were the predictor variables. RESULTS: Four equations were developed with multiple R2s that varied from .530 to .693, root mean squared errors varied from 2.8% BF to 3.4% BF, and prediction errors varied from 2.9% BF to 3.1% BF. The best equation used OD measurements at the biceps, triceps, and thigh sites, BMI, and age. The root mean squared error and prediction error for all 4 equations were equal to or smaller than for a skinfold equation commonly used with wrestlers. CONCLUSION: The results substantiate the validity of NIR for predicting % BF among high school wrestlers. Cross-validation of these equations is warranted.     

Isochromosome 7q in adult Wilms' tumors: diagnostic and pathogenetic implications

Wilms' tumors affecting adults are rare and are thought to have a worse prognosis than similar stage tumors in the pediatric population. To understand these tumors better, the authors reviewed their multi-institutional experience in a series of nine lesions diagnosed as Wilms' tumors in adults. In addition to histologic and immunohistochemical examination, they performed cytogenetic analysis and fluorescence in situ hybridization. On review, four cases were reclassified: two "blastema only" as Ewing's sarcoma/primitive neuroectodermal tumor and the other two as clear cell sarcoma of soft parts and sarcoma not otherwise specified (NOS). Of the remaining five cases, three exhibited biphasic histology and two were triphasic. In this group, there were three women and two men, and patient age ranged from 17 to 37 years (median age, 26 years). Tumor size was large and ranged from 10 to 31 cm (median tumor size, 12.5 cm). Histologically, the tumors showed the typical features of Wilms' tumors with varying amounts of blastema (n = 5), epithelium (n = 5), and stroma (n = 2). No tumors contained anaplasia, and persistent renal blastema was not identified in the non-neoplastic kidney in any specimen. All tumors were positive for cytokeratins (CK7, n = 3; pankeratin, n = 5), and one tumor was weakly positive for CD99 (0-13). Molecular analysis including dual color fluorescence in situ hybridization (all tumors), and cytogenetic analysis (n = 2) disclosed the presence of isochromosome 7q in three of five tumors whereas all tumors were diploid with respect to chromosome 12. Follow-up data ranged from 6 to 133 months (median follow-up, 82 months) with progression in only one patient who had stage IV disease with lymph node and lung metastases at presentation. The authors conclude that adult Wilms' tumor has been overdiagnosed. Most "blastema-only" tumors in adults are not Wilms' tumors, and in an adult, biphasic morphology should be the minimum criteria for their diagnosis. Using strict diagnostic criteria, adult Wilms' tumors have a relatively favorable prognosis. The characteristic findings of isochromosome 7q, lack of trisomy or tetrasomy for chromosome 12, and absence of persistent renal blastema suggest that the pathogenesis of Wilms' tumors in adults may be different than in the pediatric population. These genetic features may be helpful in distinguishing adult Wilms' tumors from other primary renal tumors.     

2. Survival Impact of HER-2/Neu, Cox-2, Urokinase Plasminogen Activator (upa), Cytokeratin 17/5,6 and other Markers with Long-Term Outcome of Early Breast Cancer. Report from the British Columbia Tissue Micro-Array Project (BCTMAP)

Tumor samples are available from over 19,600 Stage I-III breast cancer patients treated according to evolving British Columbia guidelines from 1978 to 1990. A tissue mico-array (TMA) was constructed from 930 of these patients, all of whom participated in randomized or phase II studies. Outcome was defined as 20-year Breast Cancer specific Survival (BrCaSS), with events defined as Breast Ca death. Follow up was median 17.8 years (ranges 11–28). Multiple tumor markers were tested, and results correlated with 20-year BrCaSS for markers expressed versus non-expressed. No difference in BrCaSS was found for aromatase, integrin-linked kinase (ILK), IGF-1 and Topo-isomerase-2. The negative predictive value of IHC versus FISH and ACIS-IHC versus FISH was 96 and 97%, respectively. The positive predictive value of IHC versus FISH and ACIS-IHC versus FISH was 84 and 84%, respectively. All tests, with the exception of HER-2 FISH were done by IHC. Results of other markers (VEGF, ER/PgR, hypoxia markers, etc.), and an interactive multivariate analysis adjusting for conventional prognostic factors and for all above markers, are in progress. Conclusions 1. The TMA is a technique which provides opportunity for rapid screening of multiple genetic markers.2. Expression of Her-2/Neu, uPA, Cox-2 and Cytokeratin 17/5,6 (but not of Aromatase, ILK, TOPO-II and IGF-1) is associated with inferior BrCaSS.3. HER-2 determination by ACIS-IHC provides comparable results to IHC done manually (with a potential for more uniform reporting), and both provide comparable results to Her-2 assessment by FISH. ^** ACIS-IHC:IHC red by Automated Cell Image System (M.L.)     

Metastatic Soft Tissue Sarcoma in Adults

In the present paper the treatment of advanced and metastatic soft tissue sarcoma is reviewed with the primary emphasis on chemotherapy. One of the major advances in the treatment of soft tissue sarcomas is their treatment by multidisciplinary teams in specialized centers. Despite optimal local treatment of the primary tumor, disseminated disease will develop in many patients. Consequently, chemotherapy has been extensively studied but, unfortunately, the responsiveness of these tumors to chemotherapy has been disappointingly low. Doxorubicin and ifosfamide appear to be the most effective drugs — the latter with a somewhat higher toxicity at effective dosages. Other drugs with some first line activity are dacarbazine, liposomal doxorubicin and possibly trabectedin (ET-743). Imatinib is very effective in gastrointestinal stromal tumors (GIST) where it is now the treatment of choice. The combination of doxorubicin and ifosfamide increases the response rate without affecting overall survival. For these reasons, single agent doxorubicin is, in many centers, considered the standard treatment for advanced soft tissue sarcoma, and combination chemotherapy should be reserved for special subgroups of patients such as young patients with chemosensitive tumors. Chemotherapy for patients with advanced and metastatic soft tissue sarcoma is inadequate at present and new drugs are desperately needed. Fortunately, exciting new drugs are under development and hopefully they will improve the treatment of patients with this disease.